Urothelial malignant disease and Chinese herbal nephropathy

Aristolochic acid (AA)‐DNA adduct as marker of AA exposure and risk factor for AA nephropathy‐associated cancer

“…5,6 An invasive transitional cell carcinoma of the urinary tract associated with the presence of AA-DNA adducts was also reported in an English patient with AAN. 7 This report therefore highlights once again the carcinogenic potential of AA in humans beings. Of note, herbal remedies containing species of the genus Aristolochia were recently classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC).…”

“…In patient 1, adduct levels in kidney and bladder, the target tissues for AAN-associated urothelial malignancy, were remarkably lower than in the ureter (Table I). Although the levels of dA-AAI adducts in the ureter from an English patient with AAN were 10-fold higher than in the kidney, 7 it is of interest to note that in urothelial tissues from Belgian AAN patients the levels of dA-AAI adducts were higher in renal than in ureteric tissue. 5 It is therefore tempting to speculate that other components given during the slimming regimen in Belgium may have influenced the metabolic activation and/or persistence of AA-DNA adducts in renal tissue.…”

Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:Cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid‐DNA adducts found in patients with urothelial cancer

“…2) as those obtained in vivo in rats and humans reported previously. 10,11,[17][18][19][20][21][22][23] These adduct spots formed by AAI showed the same migration on PEI-cellulose TLC plates and on reversed-phase HPLC as those of synthetic standards 19 (Fig. 3).…”

“…7,8 Recently, a high prevalence of urothelial cancer was found in a large cohort of patients suffering from aristolochic acid nephropathy in Belgium 9,10 and a case with urothelial cancer has also been described in the United Kingdom. 11 It is also noteworthy that AA consumption may be a cause for the development of a similar type of fibrosis of the kidneys with malignant transformation of the urothelium, the Balkan endemic nephropathy, [12][13][14][15] which is widely found in certain areas of Rumania, Croatia, Bosnia, Serbia and Bulgaria along the Danube river basin. [12][13][14][15] This highlights the carcinogenic potential of AA in human beings.…”

China to roll back regulations for traditional medicine despite safety concerns

“…Aristolochic acid has also been linked to cancers of the urinary tract and can cause fatal kidney damage 2,3 . Rozen says that it is still in common use, despite warnings from the US Food and Drug Administration that it is associated with kidney disease.…”